Regadenoson [(1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxalan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamine] is a selective A2A-adenosine receptor agonist that is a coronary vasodilator. It is currently marketed in the form of a monohydrate as a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.
U.S. Pat. No. 8,106,183 describes amorphous regadenoson, and three forms of regadenoson, referred to as Form A (a monohydrate), Form B and Form C.
The synthesis of regadenoson is described, for example, in U.S. Pat. Nos. 6,403,567 and 7,183,264. The syntheses disclosed are multi-step processes that proceed via 2-hydrazinoadenosine, which is prepared from the corresponding iodo-derivative (2-iodoadenosine). Although these methods are suited to small scale syntheses, they are not well suited for large scale syntheses. Moreover, the yields are low and the staining nature of iodine makes the purification of the 2-iodoadenosine intermediate problematic. It is desirable, therefore, to find new methods of synthesis that provide a convenient method for making large quantities of the material in good yield and high purity.